A diagnosis of celiac disease means the individual must stay on a strict gluten free diet for life. Following such a diet strictly is not always easy as there are many hidden sources of "gluten". A gluten free diet may also involve added cost to the individual and impact their quality of life. Therefore it is essential that the physician first confirm the diagnosis before recommending life long adherence to the diet. On the other hand it is equally important to not miss the diagnosis of celiac disease. Failure to treat an individual with celiac disease carries potential adverse long term health consequences involving both increased morbidity and mortality.
Serological tests for celiac disease have a number of potential uses. First, they may be used to identify symptomatic individuals who require an intestinal biopsy to diagnose celiac disease. This is particularly useful in those with non specific gastrointestinal complaints or with non gastrointestinal symptoms of celiac disease. Second, the tests are helpful for screening asymptomatic individuals who belong to a group considered at increased risk for celiac disease. Those with positive tests should be referred for a biopsy. Third, positive tests prior to treatment, that become negative on treatment, in an individual with characteristic changes on small intestinal biopsy are strong supportive evidence for the diagnosis of celiac disease. Fourth, tests that revert from positive to negative may provide indirect evidence that the individual is adhering to the diet. Alternatively, tests that become positive again after having become negative suggest the individual is again ingesting gluten containing products.
Commercially available tests for celiac disease include the Antigliadin, anti endomysial and anti tissue-transglutaminase tests. Tissue transglutaminase has been identified as the auto-antigen in celiac disease against which endomysial antibodies are directed. Initial transglutaminase tests used guinea pig protein as the antigen. Cloning of the gene for human transglutaminase has allowed for tests using human recombinant protein. In addition to antibody tests, some commercial laboratories are offering tests to identify the HLA DQ2 and DQ8 genotypes that are known to be strongly associated with celiac disease.
This slide illustrates the various histolopathological findings that occur in celiac disease.
J. Am. Diet. Assoc. (1994) 94(8): 874-876. This list of obstacles was adapted from a list generated by people with diabetes. The practical, social and emotional impact of a celiac diagnosis is an ever present reality for a person with the condition. No longer able to take the convenience, availability or content of food for granted, a celiac must remain armed with the knowledge of a food scientist, the savvy of a world class chef schooled in all aspects of food preparation, and the ability to anticipate and prepare for the need to bring along gluten-free alternatives for events, meetings, and dinners out. Underlying these practical matters are fears and feelings which impact health behavior. While it is normal to feel angry and overwhelmed at times, medical professionals need to monitor patients who may not be adjusting to the diagnosis as well as could be expected. Depression, anxiety, anger and fear that interfere with daily activities or lead to behaviors like removing more foods than are necessary from the diet requires additional intervention.
What you can do: State information about the disease and the patients tests in an objective manner. (Avoid guilt, pressure) Provide a prompt referral to a knowledgeable dietitian as soon as possible after diagnosis and provide information that will help reinforce or shape the patient ’s knowledge about their condition. (Physician credibility reinforces internal knowledge) Help patients learn positive coping skills by breaking down big changes into smaller steps. (recommend positive strategies) Intervene when depression or anxiety is apparent; research shows that the successful management of these conditions are crucial for adherence and adopting positive health behaviors. Reinforce internally motivated factors that are apparent in patient ’s life (a patient who feels better is experiencing an internal factor).
Celiac Disease:A Glimpse of the Future Gaetano Morelli MD 1
DefinitionCeliac disease is an immune-mediatedenteropathy caused by a permanent sensitivityto gluten in genetically susceptible individuals.It occurs in symptomatic subjects withgastrointestinal and non-gastrointestinalsymptoms, and in some asymptomaticindividuals 2
IncidenceAge of onset from 6 months to 90+ yearsAffects up to 1%, mostly Caucasians, MiddleEastern and West Asians (Indian/Pakistani)Long-term risks include Osteoporosis 2x overall mortality rate 2x risk GI tumours 3
Clinical ManifestationsGastrointestinal (“classical”)Non-gastrointestinal ( “atypical”)AsymptomaticIn addition, Celiac Disease may be associated with otherconditions, and mostly with:• Autoimmune disorders• Some syndromes 4
Celiac Disease Occurs withThe Big Three Anemia, Iron, Folate, B12 deficiency Frequent tiredness or chronic fatigue; Ongoing GI upset Diarrhea &/or constipation Abdominal pain, indigestion, bloating, gas 6
Chance of a Positive DiagnosisIncreases if the Big Three coexists with either: Thyroid disease Type I diabetes mellitus Down syndrome Abnormal liver function- transaminases especially Osteoporosis Undefined neurological disorder/epilepsy Infertility/recurrent miscarriage 7
Screen these for the Big 3Infertility (unexplained) Idiopathic ataxia orOsteoporosis neuropathyFatigue Sjogren’s syndromeSero-negative Idiopathic ataxiarheumatoid arthritis IgA deficiencyDepression Primary biliary cirrhosisFractured NOF Downs syndromeImpaired memory Turner syndromeDermatitis Liver failureherpetiformis ThyroiditisCerebral calcification Diabetes (Type 1)epilepsy Addison’s disease 8
AsymptomaticSilent LatentSilent:No or minimal symptoms, “damaged” mucosa andpositive serology Identified by screening asymptomatic individuals from groups at risk such: First degree relatives Down syndrome patients Type 1 diabetes patients, etc. 11
AsymptomaticSilent LatentLatent: No symptoms, normal mucosa May show positive serology. Identified by following in time asymptomatic individuals previously identified at screening from groups at risk. These individuals, given the “right” circumstances, will develop at some point in time mucosal changes (± symptoms) 12
Associated Conditions 20 16percentage 12 8 4 General 0 Population Relatives IDDM Thyroiditis Down syndrome 13
RelativesHealthy population: 1:1331st degree relatives: 1:18 to 1:222nd degree relatives: 1:24 to 1:39 Fasano, et al, Arch of Intern Med, Volume 163: 286-292, 2003 14
“Mines” of Celiac Disease are Found Among Relatives Patients with Associated short stature, anemia, fatigue, diseases hypertransaminasemia “Healthy” groups autoimmune disorders, Down’s, IgA deficiency, neuropathies, osteoporosis, infertility blood donors, students, general population 15
Celiac Disease Epidemiological Study in USA Population screened 13145 Healthy Individuals Risk Groups 4126 9019 Symptomatic subjects 1st degree relatives 2nd degree relatives 3236 4508 1275Positive Negative Positive Negative Positive Negative Positive Negative 31 4095 81 3155 205 4303 33 1242 Prevalence Prevalence Prevalence Prevalence 1:133 1:40 1:22 1:39 Projected number of celiacs in the U.S.A.: 2,115,954 Actual number of known celiacs in the U.S.A.: 40,000 For each known celiac there are 53 undiagnosed patients. 16 A. Fasano et al., Arch Int Med 2003;163:286-292.
Celiac Disease Icebergs10 Overall 8 Diagnosed 6 4 2 0 Ireland Italy Netherlands Sweden USA 17
The Cause of Celiac Disease HLA-DQ2 Digestion Deamidation E E T-cell IFNγ InjuryGluten Resistantproteins peptides Villous atrophy 19
HLA-DQ in Celiac Disease European Genetics Cluster on Celiac Disease; n=1007 0.4% 6.0% 5.7% DQA1*05 & DQB1*02 (HLA-DQ2) DQA1*05 or DQB1*02 DQ1*03 & DQB1*0302 (HLA-DQ8) Other 88.0% 20
HLA-DQ Genes Have Strong Negative Predictive ValueDQA1*05 or DQB1*02DQA1*0301 + DQB1*0302 Present AbsentCeliac: 99.6% 0.4%Non-celiac: 35% 65% 21
DiagnosisDiagnostic principles Confirm diagnosis before treating Diagnosis of Celiac Disease mandates a strict gluten-free diet for life following the diet is not easy QOL implications Failure to treat has potential long term adverse health consequences increased morbidity and mortality 22
Serological TestsRole of serological tests: Identify symptomatic individuals who need a biopsy Screening of asymptomatic “at risk” individuals Supportive evidence for the diagnosis Monitoring dietary compliance 23
Sensitivity and Specificity of Serologic TestsSERUM TESTS SENSITIVITY SPECIFICITY IgA EMA 85-98% 97-100% IgA tTG 90-98% 94-99% IgA AGA 75-90% 82-95% IgG AGA 69-85% 73-90% 25
Histological Features Normal 0 Infiltrative 1 Hyperplastic 2Partial atrophy 3a Subtotal atrophy 3b Total atrophy 3c 26 Horvath K. Recent Advances in Pediatrics, 2002.
Treatment Only treatment for celiac disease is a gluten-free diet (GFD) Strict, lifelong diet Avoid: Wheat Rye Barley 27
Oats –are they Safe?Studies from 1970’s suggested that oatswere toxic in CDOats contain a protein-aveninAvenin- similar to wheat gliadinBoth are prolamins –rich in glutamine andproline, both amino acids 28
OATSAvenin- proportion of proline and glutmaineis very low in oats compared to gliadin inwheat2004, Random. Clin Trial in children fedGFD vs. GFD with oats Hogberg Gut May 1, 2004 53(5)649-654. 29
FindingsFirst large study to indicate that oats in GFD donot prevent normalization of the small boweltissue or celiac markers.Other evidence supporting the safety of oats;G. Kilmartin Gut, January 1, 2003In CD, oats are not toxic and immunogenic,Srinivasan BMJ 1996:1300-01 30
Sources of Gluten OBVIOUS SOURCES Bread Bagels Cakes Cereal Cookies Pasta / noodles Pastries / pies Rolls 31
Treatment – 6 Elements in RX Consultation with a skilled dietitian Education about the disease Lifelong adherence to a gluten-free diet Identification and treatment of nutritional deficiencies Access to an advocacy group Continuous long-term follow-up by a multidisciplinary team 32
Barriers to Compliance Ability to manage emotions – depression, anxiety Ability to resist temptation – exercising restraint Feelings of deprivation Fear generated by inaccurate information 33
Factors that Improve AdherenceInternal Adherence Factors Include: Knowledge about the gluten-free diet Understanding the risk factors and serious complications can occur to the patient Ability to break down big changes into smaller steps Ability to simplify or make behavior routine Ability to reinforce positive changes internally Positive coping skills Ability to recognize and manage mental health issues Trust in physicians and dietitians 34
Approach to CD Moderate to high probability IgA TTG and duodenal biopsy+ serology + serology - serology - serology- histology + histology + histology - histology Review or Exclude other causes of Diagnosis Celiac repeat biopsy celiac-like enteritis excluded 35
Approach to CD Low probability Test for IgA TTG Positive Negative Perform biopsy CD excluded 36
ConclusionCeliac disease is common: 1% community GI symptoms are often absent or mild Fatigue, anaemia, headaches are common Celiac serology is a cheap and effective screen Gene testing can exclude celiac disease Gastroscopy and duodenal biopsy are essential Family testing is important Gluten free diet is complex - a skilled dietician is essential 37
Global Village of Celiac Disease In many areas of the world Celiac Disease is one of the commonest, lifelong disorders affecting around 1% of the general population. Most cases escape diagnosis and are exposed to the risk of complications. Active Celiac Disease case-finding is needed but mass screening should be considered. The impact of Celiac Disease in the developing world needs further evaluation. 38
Gastrointestinal Manifestations (“Classic”) Most common age of presentation: 6-24 months Chronic or recurrent diarrhea • Abdominal pain • Vomiting Abdominal distension • Constipation Anorexia • Irritability Failure to thrive or weight loss 39
Non Gastrointestinal Manifestations Most common age of presentation: older child to adult • Dermatitis Herpetiformis • Iron-deficient anemia • Dental enamel hypoplasia resistant to oral Fe of permanent teeth • Hepatitis • Osteopenia/Osteoporosis • Arthritis • Short Stature • Epilepsy with occipital • calcifications Delayed Puberty 41
Major Complications of Celiac Disease Short stature Osteoporosis Dermatitis Gluten ataxia and herpetiformis other neurological Dental enamel disturbances hypoplasia Refractory celiac Recurrent stomatitis disease and related disorders Fertility problems Intestinal lymphoma 42
EpidemiologyThe “old” Celiac Disease Epidemiology: • A rare disorder typical of infancy • Wide incidence fluctuates in space (1/400 Ireland to 1/10000 Denmark) and in time • A disease of essentially European origin 43